Hydrogen peroxide is a mediator of indole-3-acetic acid/horseradish peroxidase-induced apoptosis

• Published in: FEBS letters Vol. 580; no. 5; pp. 1439 - 1446
• Main Authors: Kim, Dong-Seok, Jeon, Sang-Eun, Jeong, Yun-Mi, Kim, So-Young, Kwon, Sun-Bang, Park, Kyoung-Chan
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 20.02.2006
• Subjects: 2,2′-azobis (2-amidinopropane) dihydrochloride; 2,7-dichlorofluorescin diacetate; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; AAPH; Apoptosis; Apoptosis - drug effects; c-Jun N-terminal kinase; Caspase 3; Caspases - metabolism; Catalase - physiology; Cell Line, Tumor; DCF; DCFH-DA; dichlorofluorescein; Free Radicals; Horseradish peroxidase; Horseradish Peroxidase - pharmacology; HRP; Humans; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; IAA; Indole-3-acetic acid; Indoleacetic Acids - pharmacology; JNK; Melanoma; Melanoma - pathology; mitogen-activated protein; MTT; NADP - pharmacology; PARP; peroxiredoxin; poly(ADP-ribose) polymerase; Poly(ADP-ribose) Polymerases - metabolism; Prx; reactive oxygen species; ROS; SOD; superoxide dismutase; Hydrogen peroxide; Indole-3-acetic acid; AAPH; DCF; JNK; HRP; Melanoma; IAA; Horseradish peroxidase; SOD; PARP; MTT; DCFH-DA; Prx; ROS; MAP; Apoptosis
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2006.01.073

Recently, we reported that a combination of indole-3-acetic acid (IAA) and horseradish peroxidase (HRP) induces apoptosis in G361 human melanoma cells. However, the apoptotic mechanism involved has been poorly studied. It is known that when IAA is oxidized by HRP, free radicals are produced, and since oxidative stress can induce apoptosis, we investigated whether reactive oxygen species (ROS) are involved in IAA/HRP-induced apoptosis. Our results show that IAA/HRP-induced free radical production is inhibited by catalase, but not by superoxide dismutase or sodium formate. Furthermore, catalase was found to prevent IAA/HRP-induced apoptotic cell death, indicating that IAA/HRP-produced hydrogen peroxide (H 2O 2) may be involved in the apoptotic process. Moreover, the antiapoptotic effect of catalase is potentiated by NADPH, which is known to protect catalase. On further investigating the IAA/HRP-mediated apoptotic pathway, we found that the IAA/HRP reaction leads to caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage, which was also blocked by catalase. Additionally, we found that IAA/HRP produces H 2O 2 and induces peroxiredoxin (Prx) sulfonylation. Consequently, our results suggest that H 2O 2 plays a major role in IAA/HRP-induced apoptosis.